New protocol streamlines therapy that makes more kidney transplants possible

Jul 17, 2008

A new therapy developed at Cedars-Sinai Medical Center improves transplant rates and outcomes for patients awaiting living- and deceased-donor kidney transplantation, according to a study published in the July 17 issue of the New England Journal of Medicine.

The therapy may provide an option for many patients "sensitized" to transplant antigens (human leukocyte antigens, or HLA) who previously would not have been candidates for transplantation because of their intense immune response to these HLA targets.

HLA exposure can come through blood transfusions, previous transplantation or pregnancy. Once exposed, the immune system is sensitized to those antigens and develops antibodies to fight them. If a donor organ with the antigens is later transplanted, the antibodies respond, increasing the risk of rejection and loss of the organ. Antibodies to HLA were previously considered an absolute contraindication to transplantation – the risk was too high for transplantation to be an option.

About 30 percent of the 74,000 patients on the transplant waiting lists for a deceased-donor kidney are sensitized, and those with exceptionally high antibody levels are considered especially poor candidates for transplantation. In fact, each year only 6.5 percent of highly sensitized patients receive a transplant. Most remain on dialysis indefinitely, without hope for a life-saving transplant.

"From a quality-of-life perspective, as well as from the financial standpoint, transplantation is a much better option than years of dialysis," said Stanley C. Jordan, M.D., director of the Division of Nephrology and medical director of the Renal Transplant Program at Cedars-Sinai. The senior author of the journal article, Jordan developed high-dose intravenous immunoglobulin (IVIG) therapy to "desensitize" highly sensitized patients and increase their chances of successful transplantation. The approach became a Medicare-approved therapy in 2004 at the conclusion of a National Institutes of Health-funded multicenter study.

Cedars-Sinai is a national leader in desensitization for the highly HLA sensitized patient, offering therapy for those awaiting both living-donor and deceased-donor transplantation.

The New England Journal article describes a Phase I/II safety and limited efficacy trial of a combination of IVIG and rituximab, a monoclonal antibody – an antibody engineered to bind to a specific protein. The combination of IVIG and rituximab appears to offer superior benefits to IVIG alone, improving transplant rates to 80 percent of treated patients. The one-year patient and graft survival rates were 100 percent and 94 percent, respectively.

Based on these results, the new protocol is less costly than IVIG alone yet appears to be highly effective in reducing antibody levels and improving transplantation rates. Larger, multicenter trials are necessary to confirm these findings.

Because nearly one-third of kidney failure patients are highly sensitized and few transplant centers specialize in desensitization therapy, many potential candidates are told that a transplant simply is not possible.

"Patients who are on dialysis and those who are progressing toward renal failure should be considered for a kidney transplant. Ideally, they would be referred to a transplant center for evaluation even before they start dialysis because data show that those who get transplanted before starting dialysis do better," Jordan said. "However, for the highly sensitized patient, transplantation is not an option unless desensitization therapies are used."

Jordan estimates that about 40 percent of Cedars-Sinai's kidney transplant patients are highly sensitized and are referred or self-referred to the program because of their highly sensitized state. For many patients, especially those awaiting a deceased-donor transplant, the combination of IVIG and rituximab appears to offer an alternative to ongoing dialysis.

The New England Journal of Medicine article is accompanied by an editorial written by Ron Shapiro, M.D., of the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh. He concludes his comments by saying, "As the authors note, their observations need to be confirmed and validated by other centers and in larger numbers of patients and during longer periods of follow-up. However, their approach may represent a breakthrough in the care of sensitized patients awaiting transplantation and may have the potential to help thousands of patients who are languishing on waiting lists around the world."

Source: Cedars-Sinai Medical Center

Explore further: Experts call for higher exam pass marks to close performance gap between international and UK medical graduates

add to favorites email to friend print save as pdf

Related Stories

Japan lab says stem cell research falsified (Update 3)

Apr 01, 2014

The finding that a lead researcher falsified data in a widely heralded stem-cell research paper is a setback for Japan's efforts to promote its advanced research, but also a symptom of the pressure for breakthroughs ...

Embryonic stem cells: Reprogramming in early embryos

Mar 26, 2014

An Oregon Health & Science University scientist has been able to make embryonic stem cells from adult mouse body cells using the cytoplasm of two-cell embryos that were in the "interphase" stage of the cell ...

Research team implants human innate immune cells in mice

Mar 18, 2014

(Phys.org) —Overcoming a major limitation to the study of the origins and progress of human disease, Yale researchers report that they have transplanted human innate immune cells into mouse models, which ...

An end to animal testing for drug discovery?

Mar 18, 2014

As some countries and companies roll out new rules to limit animal testing in pharmaceutical products designed for people, scientists are stepping in with a new way to test therapeutic drug candidates and determine drug safety ...

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.